Background

Flavonoids have been demonstrated to have the ability of sensitizing cancer cells to chemotherapy and inverse multidrug resistance via various mechanisms, such as modulating of pumps. The therapeutic effect of candidone, tephrosin, and bavachinin in treatment of cancer, particularly to overcome multidrug resistance (MDR) is largely unknown. The capacity of these agents in sensitization of MDR cells is investigated in the current work.

Methods and results

We analyzed the impact of candidone, tephrosin, and bavachinin, as chemosensitizer on cell cytotoxicity, P-gp and ABCG2 mRNA expression level on two multidrug resistant cells, ABCG2 overexpressing human epithelial breast cancer cell line (MCF7/MX), and P-gp overexpressing human gastric adenocarcinoma cell line (EPG85.257RDB). The inhibitory concentration of 50% (IC50) of daunorubicin in EPG85.257RDB cells in combination with IC10 of Bavachinin, Tephrosin, and Candidone were 6159 ± 948, 4186 ± 665, 730 ± 258 nM, and this data in MCF7/MX cell were 1773 ± 534, 7160 ± 405 and 3340 ± 622 nM respectively. These three flavonoids dose-dependently decreased the viability of MCF7/MX and EPG85.257RDB and significantly (p < 0.05) decreased IC50 of daunorubicin and mitoxantrone except Tephrosin in MCF7/MX cells. Candidone and Bavachinin were the most potent chemosensitizer in EPG85.257RDB and MCF7/MX cells respectively. Flavonoids did not reduce mRNA expression of P-gp and ABCG2 after 72 h treatment, except Candidone in EPG85.257RDB and Bavachinin in MCF7/MX cells.

Conclusions

This effect is not time-dependent, and flavonoids have their own patterns that are cell-dependent. In general, tephrosin, candidone, and bavachinin had the potential of sensitizing MDR cells to mitoxantrone and daunorubicin.

中文翻译：

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Candidone、tephrosin 和 bavachinin 改善米托蒽醌和柔红霉素的细胞毒性

背景

黄酮类化合物已被证明具有使癌细胞对化疗敏感的能力，并通过各种机制（例如调节泵）逆转多药耐药性。candidone、tephrosin 和 bavachinin 在癌症治疗中的治疗效果，特别是在克服多药耐药性 (MDR) 方面的疗效在很大程度上是未知的。在目前的工作中研究了这些药物在 MDR 细胞致敏中的能力。

方法和结果

我们分析了 candidone、tephrosin 和 bavachinin 作为化学增敏剂对细胞毒性、P-gp和ABCG2的影响两种多重耐药细胞上的 mRNA 表达水平，ABCG2 过表达人上皮乳腺癌细胞系 (MCF7/MX) 和 P-gp 过表达人胃腺癌细胞系 (EPG85.257RDB)。EPG85.257RDB 细胞中 50% (IC50) 柔红霉素的抑制浓度与 Bavachinin、Tephrosin 和 Candidone 的 IC10 组合为 6159 ± 948、4186 ± 665、730 ± 258 nM，而在 MCF7/MX 细胞中的该数据为分别为 1773 ± 534、7160 ± 405 和 3340 ± 622 nM。这三种黄酮类化合物剂量依赖性地降低了 MCF7/MX 和 EPG85.257RDB 的活力，并且显着（p < 0.05）降低了 MCF7/MX 细胞中柔红霉素和米托蒽醌的 IC50，除了 Tephrosin。Candidone 和 Bavachinin 分别是 EPG85.257RDB 和 MCF7/MX 细胞中最有效的化学增敏剂。

结论

这种效果不依赖于时间，并且类黄酮有自己的细胞依赖模式。一般而言，tephrosin、candidone 和 bavachinin 具有使 MDR 细胞对米托蒽醌和柔红霉素敏感的潜力。